Composition for treating a disease caused by neuronal insult comprising a human umbilical cord blood-derived mesenchymal stem cell as an active ingredient

a technology of umbilical cord blood and stem cells, applied in the direction of biocide, drug composition, nervous disorder, etc., can solve the problems of cell engraftment and survival ability degrade, secondary injury, and difficulty in implementing cell engraftment or cell survival, so as to confirm the therapeutic effect of nerve damage-related diseases, the effect of improving the recovery of behavior motor ability and facilitating the migration of transplanted cells to the lesion area

Inactive Publication Date: 2008-06-05
THE CATHOLIC UNIV OF KOREA IND ACADEMIC COOP FOUND
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

[0013]It was surprisingly found that in vivo administration of the human umbilical cord blood-derived mesenchymal stem cell has a therapeutic effect on nerve damage-related diseases (stroke, spinal cord injury disease).
[0014]Particularly, it was confirmed that, when the cell is transplanted to the rostral area of the injured area, rather than the epicenter and caudal areas, behavioral motor ability recovery was better and migration to the lesion area and engraftment of the transplanted cells were higher.
[0015]As described above, the present inventors have completed the present invention by confirming the therapeutic effect on nerve damage-related diseases by means of in vivo administration of the mesenchymal cells, particularly, the human umbilical cord blood stem cell. The present inventors have analyzed in detail and proved the therapeutic effect on nerve damage-related diseases by means of in vivo administration of the mesenchymal stem cells in medical or biological experiments.

Problems solved by technology

However, it is reported that, cell engraftment and survival ability may be degraded by a micro-environment of the injured area when the cells are directly transplanted to the epicenter of the injury, and secondary injury may occur when the cells are transplanted to the rostral.
In addition, it is reported that it is difficult to implement cell engraftment or cell survival and migration to the injured area due to an already broken nerve path when the cells are transplanted to the caudal of the injured area.

Method used

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  • Composition for treating a disease caused by neuronal insult comprising a human umbilical cord blood-derived mesenchymal stem cell as an active ingredient
  • Composition for treating a disease caused by neuronal insult comprising a human umbilical cord blood-derived mesenchymal stem cell as an active ingredient
  • Composition for treating a disease caused by neuronal insult comprising a human umbilical cord blood-derived mesenchymal stem cell as an active ingredient

Examples

Experimental program
Comparison scheme
Effect test

embodiments

First Embodiment

Experiment using a Spinal Cord Injury Model of White Rat

[0060]1. Material and Method

[0061]1.1. Separation of Human Umbilical Cord Blood-Derived Mesenchymal Stem Cell

[0062]Human umbilical cord blood obtained with parental consent were separated by Ficol gradient (density 1.077 g / cm3, Sigma Co.) to clean mononuclear cells, which were then suspended by α-MEM (Gibco BRL) contained with 10% FBS (HyClone) and divided at a concentration of 5×106 cells / cm2. An incubating solution was exchanged two times a week, and the cells were incubated with 5% CO2 at 37° C.

[0063]When incubation of mononuclear cells derived from the human umbilical cord blood was established and fibro blast like adhesive cells were observed, 0.25% Trypsin (HyClone) was processed to separate cells and then was suspended again by an incubating solution when a monolayer of colonies was 80% after three weeks.

[0064]After the cells were secondarily incubated with a dimension of 5×104 cells / cm2, they were in vit...

second embodiment

Effect of Human Umbilical Cord Blood-Derived Mesenchymal Stem Cell on Endogenous Neurogenesis of Spinal Cord Injury of Contused Mature White Rat

[0096]In the present embodiment, it was checked 1) whether the transplanted hUCB-derived MSCs can improve a function outcome of the mature rat having the contusive spinal cord injury (SCI), 2) whether the hUCB-derived MSCs can be differentiated and expressed into a nerve or neuroglial cell and 3) whether the hUCB-derived MSCs derive the expression of the neurotrophic facto regenerated after SCI or proliferation of intrinsic endogenous neural stem / progenitor cells.

[0097]After the human umbilical cord blood-derived mesenchymal stem cell was separated in accordance with the method of FIG. 5 and transplanted, intraperitoneally BrdUrd (50 mg / kg, Sigma-Aldrich) was injected into the SD rat for labeling a newly generated cell for 14 days. Then, the checked proliferation reaction is focused on cytogenetics in which cells are generated within 14 days...

third embodiment

Effect of Human Umbilical Cord Blood-Derived Mesenchymal Stem Cell on Treatment of Stroke in a White Rat

[0110]In the present embodiment, a functional test, migration to the injured area, and differentiation into a nerve cell after UCB-MSCs transplantation will be described.

[0111]Focal cerebral ischemia was derived by intraluminal thread occlusion of middle cerebral artery (MCA). At the seventh day of transplantation, the PKH-26 labeled UCB-MSCs (3×105 cells / 5 μl) were transplanted to the injured cerebrum contralateral lesion of the rat.[0112]Focal cerebral ischemia model

[0113]Sprague-Dawley male (rat weight): 230-250 g

[0114]An intraluminal filament technique (Middle cerebral artery occlusion; MCAO) was performed on transient focal cerebral ischemia.

[0115]4-0 monofilament suture; round end

[0116]120 minutes MCA occlusion; a heating pad was used to remain at 37° C.[0117]MCAO rotarod test

[0118]Adhesive-removal test: ¢ 12, 113.1 mm2 paper dot

[0119]Rotarod test; 4-40 rpm, accelerated test...

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Abstract

Provided is a composition for treating nerve damage-related diseases. The composition includes a human umbilical cord blood-derived mesenchymal stem cell as an active ingredient. The mesenchymal stem cell isolated and incubated from the human umbilical cord blood migrates to an injured area to be differentiated into a nerve cell or a neuroglial cell at the time of in vivo transplantation. Thus, the mesenchymal stem cell and a composition including the same can be effectively used in cell replacement therapy and gene therapy for treating diseases caused by nerve damage including a stroke, Parkinson's disease, Alzheimer's disease, Pick's disease, Huntington's disease, amyotrophic lateral sclerosis, traumatic central nervous system disease and a spinal cord injury.

Description

CROSS-REFERENCE TO RELATED APPLICATION[0001]This application claims the benefit of Korean Patent Application No. 2006-0120227, filed Nov. 30, 2006, the contents of which are hereby incorporated herein by reference in their entirety.BACKGROUND OF THE INVENTION[0002]1. Field of the Invention[0003]The present invention relates to a composition for treating nerve damage-related diseases comprising a human umbilical cord blood-derived mesenchymal stem cell as an active ingredient.[0004]2. Description of the Related Art[0005]Traumatic spinal cord injury, one type of injury resulting in difficult-to-cure damage to the nervous system, produces an excitotoxicity neurotransmitter1, a free radical2, an inflammation promoting medium3, and so forth. These give rise to apoptosis of nerve cells and neuroglial scars are formed, which creates an environment that inhibits nerve regeneration. Treatment for such spinal cord injury focuses on development of material which activates genes associated with...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): A61K35/00A61P25/00A61K35/28
CPCA61K35/28A61P25/00A61P25/28A61K9/0019A61K35/51
Inventor JEUN, SIN SOO
Owner THE CATHOLIC UNIV OF KOREA IND ACADEMIC COOP FOUND
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